TP53 mutations in breast cancer: association with ductal histology and early relapse of disease.
OBJECTIVE
This study aimed to investigate the incidence of core domain TP53 mutations in Serbian breast cancer patients in view of their possible correlation with prognostic parameters, tumor characteristics and clinical disease course.


METHODS
145 breast cancer patients were included. Data on clinical disease course were available for 100 patients including 30 node-negative and 70 node-positive patients. After surgery, node-positive patients underwent adjuvant chemotherapy, mostly CMF. TP53 mutations were detected by PCR-SSCP.


RESULTS
31 mutations were found in 27/145 patients including 4/59 node-negative patients and 23/83 node-positive patients (4 double mutations). 26/31 TP53 mutations were found in patients with invasive ductal carcinoma and only 2 in patients with invasive lobular carcinoma. The presence of TP53 mutations was correlated with clinical disease course in premenopausal node-positive patients (n=70). 11/20 patients with TP53 mutations relapsed. Within the first 24 months of follow-up, significantly shorter disease-free intervals were observed in TP53-mutated patients.


CONCLUSIONS
TP53 mutations correlated only with nodal status and ductal histology. The significance of the predominant distribution of TP53 mutations in tumors with a ductal histology for the aggressive behavior of these tumors has yet to be proved, since the favorable biological features of tumors with a lobular histology do not result in a better prognosis. Early relapse in mutated-TP53 carriers may support data on its predictive value with respect to adjuvant CMF.
Brankovic-Magic
M V
MV
Institute for Oncology and Radiology of Serbia, Belgrade - Serbia. brankovicm@ncrc.ac.yu
Jankovic
R N
RN
Dobricic
J D
JD
Borojevic
N D
ND
Magic
Z M
ZM
Radulovic
S S
SS
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D016158:Genes, p53; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011987:Receptors, Steroid / Q000378:metabolism; D012008:Recurrence; D055771:Serbia; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D011987:Receptors, Steroid; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53